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  • 1
    Electronic Resource
    Electronic Resource
    Disopyramide pharmacokinetics and bioavailability following the simultaneous administration of disopyramide and14C-disopyramide (1984)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 12 (1984), S. 289-313 
    Details
    ISSN: 1573-8744
    Keywords: protein binding ; pharmacokinetics ; bioavailability ; disopyramide ; heart failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics and bioavailability of total (bound plus unbound) and unbound disopyramide were compared following the simultaneous administration of an oral dose of disopyramide and an intravenous dose of14C-disopyramide in five normal volunteers and in 11 patients with congestive heart failure. The binding of disopyramide varied between 60 and 92% in patients and between 81 and 88% in normal subjects at postequilibrium drug concentrations of 10−7M. The binding of disopyramide to serum protein was concentration-dependent in all study subjects at serum concentrations achieved following drug administration. The association constant for the first binding site in serum from normal subjects and patients averaged 8.7X105 M−1 and 4.4X10 5 M−1, respectively (p 〈 0.05). The unbound clearance of disopyramide averaged 277ml/min and 209 ml/min in normal subjects and in patients (p 〈 0.05). When normalized for body weight, the unbound clearance between patients and normal subjects was not significantly different. The elimination half-life of unbound concentrations in normal subjects and in patients averaged 4.9 and 6.1 h, respectively (p 〈 0.05). The clearance and elimination half-life of total disopyramide was the same in both groups. Although the bioavailability of disopyramide averaged 0.85 in both groups, it was more variable in patients owing to the variability in the fraction of the dose absorbed. The unbound renal clearance and volume of distribution at steady state of disopyramide was related to cardiac index. The ratio of elimination half-lives of total and unbound disopyramide was related to the extent of serum protein binding.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01061722
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  • 2
    Electronic Resource
    Electronic Resource
    Receptor-mediated methylprednisolone pharmacodynamics in rats: Steroid-induced receptor down-regulation (1992)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 20 (1992), S. 333-355 
    Details
    ISSN: 1573-8744
    Keywords: methylprednisolone ; methylprednisone ; pharmacodynamics ; steroid receptor ; down-regulation ; tyrosine aminotransferase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Several approaches to receptor down-regulation were examined to extend previous receptor/ genemediated pharmacokinetic/dynamic models of corticosteroids. Down-regulation of the glucocorticoid receptor was considered as an instantaneous event or as a gradual steroid-receptor-mediated process. Concentrations of plasma methylprednisolone, free hepatic cytosolic receptors, and the activity of hepatic tyrosine aminotransferase (TAT) enzyme were measured for 16 hr following administration of 0, 10, and 50 mg/kg methylprednisolone sodium succinate to 93 adrenalectomized rats. Receptor down-regulation was best described by a fractional decrement in the rate of return of free cytosolic glucocorticoid receptor. Predicted values for free receptor, bound receptor, nuclear bound receptor, and transfer compartments were in accord with the expected rank order values based on the high and low steroid doses. Model parameter estimates were independent of dose and described the rapid depletion of free cytosolic receptor, latephase return of cytosolic receptor to a new baseline level that was 20–40% lower than control, and the TAT induction/dissipation pattern following steroid dosing. The microscopic association and dissociation constants describing the steroidreceptor interaction were 0.23 L/nmole per hr (kon and 4.74 hr−1 (koff) for methylprednisolone compared to previously obtained values of 0.20 L/nmole per hr and 15.7 hr−1 for the related steroid prednisolone. The time course of TAT induction was similar to that observed previously for prednisolone. Efficiency of TAT induction was more closely related to steroid receptor occupancy than plasma methylprednisolone concentrations due to receptor saturability and receptor recycling.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01062462
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Liquid Chromatographic Analysis of Di(2-ethylhexyl) Phthalate: Application to Pharmacokinetic Studies in the Mongrel Dog (1988)
    Springer
    Pharmaceutical research 5 (1988), S. 10-15 
    Details
    ISSN: 1573-904X
    Keywords: di(2-ethylhexyl) phthalate ; liquid chromatographic (LC) analysis ; pharmacokinetics ; renal failure ; mongrel dog
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A high-performance liquid chromatographic (HPLC) assay was developed for the determination of di(2-ethylhexyl) phthalate (DEHP) in serum or plasma. Plasma DEHP concentrations that were measured by HPLC in specimens obtained from hemodialysis patients were in good agreement with corresponding concentrations that were measured by gas chromatography with selected ion monitoring (GC-SIM) (r 2 = 0.996). Plasma DEHP concentrations were measured after intravenous DEHP administration (1.2–4.4 mg DEHP/kg body weight) to determine the effect of bilateral ureteral ligation on DEHP elimination in the mongrel dog. DEHP plasma clearance (∼6.3 ml/min/kg), steady-state distribution volume (∼0.2l/kg), and terminal half-life (∼50 min) were unchanged in two dogs following bilateral ureteral ligation. DEHP terminal half-life and steady-state distribution volume were substantially smaller (25- to 70-fold) than reported previously in the rat or dog.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015872309411
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    Paper (German National Licenses)
    Fulltext
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